THE LANCET, Volume 368: Page 1236,
October 7 2007.

Cautious optimism for new HIV/AIDS prevention
strategies

The 2006 International AIDS Conference,
showcased in the special (Lancet)Red issue,
was filled with promises for effective prevention strategies.
Media attention and plenary speeches suggested that effective
strategies, notably male circumcision and pre-exposure
prophylaxis (PREP), are imminent.1 Instead we advise cautious
optimism.

The inferences drawn
from the only completed randomised controlled trial (RCT) of
circumcision could be weak because the trial stopped
early.2 In a systematic
review of RCTs stopped early for benefit,3 such RCTs were found to overestimate
treatment effects. When trials with events fewer than the
median number (n=66) were compared with those with event
numbers above the median, the odds ratio for a magnitude of
effect greater than the median was 28 (95% CI 11–73).
The circumcision trial recorded 69 events, and is therefore
at risk of serious effect overestimation.

We therefore advocate an impartial
meta-analysis of individual patients’ data from this
and other trials underway before further feasibility studies
are done.

Although the rationale for PREP is exciting,
researchers have leapt from small (n=6–18) and
inconsistent nonrandomised monkey studies into multicentred
trials.4 The first PREP trial
results were provided at the conference,5 but had an insufficient number of
infections to provide any inferences about effectiveness (two
of 363 vs six of 368).

New interventions are required to slow the
HIV/AIDS pandemic. Disappointments stemming from media hype
and misinterpretation of early trials can make policy and
recruitment of appropriate trial populations difficult. If we
are to alter the epidemic’s progress, we should be
methodologically rigorous, and cautiously optimistic about
the potential for new interventions.